Abstract
Antisense technology, which is based on a simple and rational principle of Watson-Crick complementary base pairing of a short oligonucleotide with the targeted mRNA to downregulate the diseasecausing gene product, has progressed tremendously in the last two decades. Antisense oligonucleotides targeted to a number of cancer-causing genes are being evaluated in human clinical trials. While the firstgeneration phosphorothioate antisense oligonucleotides are in clinical trials, a number of factors, including sequence motifs that could lead to unwanted mechanisms of action and side effects, have been identified. The severity of the side effects of first-generation antisense oligonucleotides is mostly dependent on the presence of certain sequence motifs, such as CpG dinucleotides. A number of second-generation chemical modifications have been proposed to overcome the limitations of the first-generation antisense oligonucleotides. The safety and efficacy of several second-generation mixed-backbone antisense oligonucleotides are being evaluated in clinical trials. The immune stimulation affects observed with CpG-containing antisense oligonucleotides are being exploited as a novel therapeutic modality, with several CpG oligonucleotides being evaluated in clinical trials. A number of medicinal chemistry studies performed to date suggest that the immunomodulatory activity of CpG oligonucleotides can be fine-tuned by site-specific incorporation of chemical modifications in order to design disease-specific oligonucleotide therapeutics.
Current Cancer Drug Targets
Title: Antisense and/or Immunostimulatory Oligonucleotide Therapeutics
Volume: 1 Issue: 3
Author(s): Sudhir Agrawal and Ekambar R. Kandimalla
Affiliation:
Abstract: Antisense technology, which is based on a simple and rational principle of Watson-Crick complementary base pairing of a short oligonucleotide with the targeted mRNA to downregulate the diseasecausing gene product, has progressed tremendously in the last two decades. Antisense oligonucleotides targeted to a number of cancer-causing genes are being evaluated in human clinical trials. While the firstgeneration phosphorothioate antisense oligonucleotides are in clinical trials, a number of factors, including sequence motifs that could lead to unwanted mechanisms of action and side effects, have been identified. The severity of the side effects of first-generation antisense oligonucleotides is mostly dependent on the presence of certain sequence motifs, such as CpG dinucleotides. A number of second-generation chemical modifications have been proposed to overcome the limitations of the first-generation antisense oligonucleotides. The safety and efficacy of several second-generation mixed-backbone antisense oligonucleotides are being evaluated in clinical trials. The immune stimulation affects observed with CpG-containing antisense oligonucleotides are being exploited as a novel therapeutic modality, with several CpG oligonucleotides being evaluated in clinical trials. A number of medicinal chemistry studies performed to date suggest that the immunomodulatory activity of CpG oligonucleotides can be fine-tuned by site-specific incorporation of chemical modifications in order to design disease-specific oligonucleotide therapeutics.
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Cite this article as:
Sudhir Agrawal and Ekambar R. Kandimalla , Antisense and/or Immunostimulatory Oligonucleotide Therapeutics, Current Cancer Drug Targets 2001; 1 (3) . https://dx.doi.org/10.2174/1568009013334160
DOI https://dx.doi.org/10.2174/1568009013334160 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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